There appear to be three, perhaps independent, means by which cells can regulate the rate, the extent and the pattern of phosphorylation of the acidic proteins in their nuclei: a) by increasing the concentration of nuclear protein kinases; b) through stimulation of nuclear protein kinase activity by polyamines; and c) by elevating their c-AMP levels. These mechanisms will be explored in detail. Using specific antibodies, the de novo synthesis of the protein kinases will be followed during the embryonic development of rat liver, in hepatoma and in cultured cells. Efforts will be made to identify the factors that regulate their synthesis. It will be ascertained whether the stimulation of nuclear protein kinases by polyamines occurs independently of the effects of polyamines on cytoplasmic reactions. The effect of c-AMP on the extent and pattern of phosphorylation of nuclear proteins will be re-examined in cultured cells and in isolated nuclei prepared by a method minimizing exchanges of macromolecules between nucleus and cytoplasm. The possibility of a c-AMP-dependent translocation of cytoplasmic protein kinase into the nucleus will be explored.